Parasiticide



Patented Oct. 26; 1937 PARASITICIDE Lewis W. Butz, Chalfont, and WilliamA. La Lande, Jr., Philadelphia, Pa., assignors to Dr. D. Jayne & Son,Inc., Wilmington, Del., a corporation of Delaware No Drawing.Application June 13, 1935, Serial No. 26,522

2 Claims.

This invention relates to parasiticides, more particularly to new andimproved compositions adapted to effect the removal of internal animalparasites from host animals, including man. Animal parasites" is heredefined as all parasitic organisms exclusive of plants and bacteria.

It is known that amebas, worms and other protozoa and metazoa infest thegastro-intestinal tract as well as other sites in the body. Numerouspreparations designed to kill or eliminate such parasites have beenproposed, these being known as amebicides,- anthelmintics, or ingeneral, parasiticides. A number of such preparations have met withsuccess, but they have been highly specific in their action in the sensethat only a limited group or even only one species in a group ofparasites is affected. Moreover most of these have been shown to behighly toxic to the host. Probably two of the best known remediesheretofore used are oil of chenopodium (active component, ascaridole)and tetrachlorethylene.

The term vermicide is used in the claims to designate the compositionsand the remedial effects contemplated by this invention and referred toin this application. The term vermicide is used in its accepted meaningand can be defined as an anthelmintic drug or medicine destructive tointestinal animal parasites. Such parasites, specifically, are thosereferred to above and include but are not limited to those mentionedspecifically in the description of this application.

With a' view to advancing the development of the art of parasiticides,researches have been conducted resulting in the inventions anddiscoveries set forth in the following specification. It is an object ofthe invention to provide new and improved antiparasitic compounds. Oneimprovement in view is that new remedies shall be less specific in theirapplication than those hitherto proposed. Since the parasites envisagedin this invention exist in environments practically free of oxygen andare harmfully affected by oxygen in certain active forms,-the desiredgenerality of the drug efiect is aimed to beaccomplished by theapplication of remedies supplying oxygen in suitable form and amount.The invention, then, has for its further objects the use of new andimproved antiparasitic compounds containing oxygen in such suitableform, and particularly ozonized organic compounds or mixtures containingthese.

The compounds found to be particularly useful according to the presentinvention are organic ozonides, which term is to be understood toinclude the products obtained by passing ozone into organic compounds ormixtures containing such compounds. This class is understood to compriseall products obtained by ozonizing or ganic compounds containing doubleor triple bonds between carbon atoms and in addition a product obtainedby ozonizing mixtures containing such compounds such as mineral,vegetable and animal oils.

The use of oil of chenopodium has been established as an efficientantiparasitic remedy in infestations of human beings and lower animals.The remedial effect of this oil has been shown to be due to the organicperoxide, ascaridole, which it contains.

It is probable that the therapeutic effect of ascaridole is due, in partat least, to the peroxide group which it contains. This compound howevercontains other important groupings; namely, the olefin linkage and thepara-menthene structure. Possibly because of these latter structuralunits this peroxide is quite toxic for human beings and lower animals.The use of chenopodium oil is unsafe in view of its high toxicity whenadministered in doses sufliciently large and frequent to produce itsanti-parasitic effect. This invention has for one of its objects thetherapeutic use of ozonized organic materials as suitable sources ofoxygen in active form. We have studied a number of ozonides asanthelmintics,

These materials were tested upon Ascaris lumbricoz'des in beaker testsand upon dogs infested with Torocara cams. Ascaris Zumbrzcoides waskilled by the following: ozonized olive oil, ozonized cottonseedoil,ozonized ethyl oleate,ozonized oleic acid, ozonized geranyl acetate,andozonized methylheptenone. assay with Ascaris lumb'ricoides is asfollows:

Bioassa'J The efiect of the anthelmintic activity toward A typicalexample of a bio- 45 Ascaris lumbrz'coz'des was determined by immer- 50sion of vigorous specimens in a solution or emulsion of the substancebeing tested. The apparatus was-a rectangular aquarium with glasswindows which was filled with 'water and served as a constanttemperature bath. The temperature was maintained between 37 C. and 38 C.The aquarium was provided with a metal cover containing holes whichsupported 400 cc. beakers. Five worms were placed in each beaker whichcontained 300 cc. of solution or emulsion. The worms were 22-24 cm. inlength and weighed 2.0-2.35 gms. They were A. lumbricoides obtained fromthe intestines of swine. Observation was made after the immersion of thenumber of minutes required to produce cessation of movement, paralysisand death and were conducted at hourly intervals for a period of fivehours.

To illustrate the 'results obtained in canine Ascarzasz's data are heregiven for ozonized cottonseed oil and ozonized olive oil.

The therapeutic experiments with dogs were conducted as follows: Dogsinfested with Toxocam cam's were observed over a period of seven totendays during which time the rate of elimination of worms was determined.The ozonides were then administered in gelatin capsules and the animalsobserved for varying periods of time and finally sacrificed. The numberof worms passed after treatment and the number found at autopsy wererecorded. In this way data. shown in the following tables was secureddescribing (l) the percentage of worms present which were removed bytreatment in a large number of dogs, and (2) the rate of elimination ofworms before and after treatment. In all experiments the animalsreceived only one dose of ozonide without any solvent and withoutadministration of any other medicaments such as laxatives.

TABLE I Percentage of worms removed Dose 33 Worms Worms Percent Drug mmpresrere- (glkg) mals ent moved moved Ozonized cottonseed oiL- 0. 2 2 2928 96 7 In 8 out of 9 dogs 100 percent of the worms were removed.

TABLE II Rate of elimination of worms before and after treatment withozonized cottonseed oil Rate elimi- Dose Cure natcd (worms/ of 233222ehml' 1 Dog No.

(gJ gJ Percent Before After Before After gg Experiments have beenconducted to assure that effective doses of ozonized cottonseed oil,ozonized olive oil and ozonized ethyl oleate can be tolerated by theinfested animals. The lowest doses given were 0.2 and 0.5 g./kg. andthese were therapeutically efiective (Table I). Dogs which received 5.0g./kg. showed no symptoms of .intoxication whatever, even when the dosewas thrice repeated. The therapeutic index of ozonized cottonseed oil istherefore at least 5.0/0.2 or 25.0. In control experiments the sameindex for chenopodium oil was shown to be 8.0, and the animals werevisibly poisoned by even smaller I LEWIS W. BUTZ. WILLIAM A. LA LANDE,JR.

